The role of p53 dependent and cooperating pathways in pluripotency induction

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Reprogramming of somatic cells into induced pluripotent stem cells (iPS cells) can serve as an experimental system to understand basic mechanisms in stem cell biology, including mechanisms that facilitate or restrict pluripotency. Previous studies have shown that p53 deletion can strongly increase iPS formation and can also enhance the self-renewal of adult stem cells. p53 dependent mechanisms that control pluripotency remain yet to be defined. Using the iPS system, genetic mouse models and lentiviral shRNA libraries we will focus on following main aims: (i) Define the role of p53 dependent DNA damage checkpoints in pluripotency induction, (ii) Determine whether p53 contributes to the regulation of pluripotency pathways, (iii) Identify pathways that cooperate with p53 during pluripotency induction. The project will increase our understanding of pluripotency induction, specifically the role of p53 dependent mechanisms in this process.